The question of how neurons control behavior is central to understanding the physiological bases of mental illness. The complete description of the morphology and synaptic connectivity of all 302 neurons in the nematode C. elegans raised the prospect of the first comprehensive understanding of an entire nervous system. The long-term objective of the proposed research is to understand the neuronal basis of behavior in this model system. The present proposal focuses on a single behavior: chemotaxis, the ability of an animal to direct its locomotion up (or down) a chemical gradient. In C. elegans, this problem provides an unusual opportunity to integrate four different levels of analysis: genetics, electrophysiology, modeling, and behavior. The chemotaxis behavior of selected genetic mutations will be studied using an automated tracking system to probe the behavioral mechanism of orientation to chemical stimuli. Electrophysiological recordings will be made from neurons in normal and mutant animals to determine how chemosensory information is encoded and the molecular basis of this process. This information will be used to construct a computer model of the neural network for chemotaxis. The model will be analyzed to generate hypotheses as to the neural basis of chemotaxis. These hypotheses will be tested by further electrophysiological recordings and by studying the effects on model and real animals of eliminating specific neurons in the chemotaxis network. What is learned from studies of chemotaxis will serve as the basis for tackling other behaviors in the repertoire of C. elegans.